The present invention, in some embodiments thereof, relates to combined treatment for nerve injury.
Central nervous system (CNS) injuries such as spinal cord injury (SCI) have no successful treatment to date. SCI is associated with an immediate loss of sensory and motor locomotion with permanent deficit in reflex functions below the level of injury. Furthermore, CNS injuries are usually characterized by total failure to regenerate and heal. Immediate events which occur following SCI include ischemia, an immune response activating microglia cells and infiltration of injured cells from the neighboring vascular tissues, due to apoptotic and necrotic damages to capillary blood vessels. The injury is simultaneously accompanied by nonspecific reactive changes of glial cells e.g. astrocytes and macrophages in response to the damage including secretion of connective tissue matrix substances such as proteoglycans (PGs), collagens and myelin-derived residues. These substances lead to formation of a scar tissue resulting in inhibition of axons sprouting and restricting neuronal regeneration. Indeed, scientific reports describe treatment with anti-gliotic agents such as chondroitinase ABC to induce improvement in the synaptic plasticity and regeneration parameters (e.g. Bradbury E J et al., Nature. 11; 416(6881):636-40, 2002; and Barritt A W et al., J Neurosci. 18; 26(42):10856-67, 2006).
Hydrated gels (hydrogels) are viscous, semisolid entities at physiological temperatures and pH which can be used for tissue engineering and regenerative medicine. For example, hyaluronic acid-based hydrogels provide a growth supportive milieu for cells and tissues such as for nerve regeneration (Suzuki et. al., 2003; Itoh et. al., 2005), while guiding migration and regeneration of nutritional-trophic and anti-oxidative agents.
International Patent Application Publication No. WO2009/022339 discloses the use of a hyaluronic acid-based hydrogel containing the anti-oxidant sodium dismutase and a laminin peptide for neural tissue regeneration and repair.